1-182576254-AC-A
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_021133.4(RNASEL):c.2039+1del variant causes a splice donor change. The variant allele was found at a frequency of 0.0000789 in 1,610,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000078 ( 0 hom. )
Consequence
RNASEL
NM_021133.4 splice_donor
NM_021133.4 splice_donor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.80
Genes affected
RNASEL (HGNC:10050): (ribonuclease L) This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BS2
?
High AC in GnomAd4 at 14 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEL | NM_021133.4 | c.2039+1del | splice_donor_variant | ENST00000367559.7 | |||
RNASEL | XM_047427096.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEL | ENST00000367559.7 | c.2039+1del | splice_donor_variant | 1 | NM_021133.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 249362Hom.: 0 AF XY: 0.000149 AC XY: 20AN XY: 134598
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GnomAD4 exome AF: 0.0000775 AC: 113AN: 1457978Hom.: 0 Cov.: 30 AF XY: 0.0000924 AC XY: 67AN XY: 724838
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GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Prostate cancer, hereditary, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The splice donor variant c.2039+1del) in RNASEL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has 0.01% allele frequency in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. LOF in this gene have not been reported previously. For these reasons, this variant has been classified as Uncertain Significance. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
DS_DL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at